Transport by epithelia with compliant lateral intercellular spaces: asymmetric oncotic effects across the rat proximal tubule

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Abstract
Mathematical models of the proximal tubule are considered in which the lateral intercellular spaces distend in response to increased interstitial pressures and basal outlet permeabilities increase as a result of interspace widening. An approximate analytical model of the interspace reveals the possibility that such compliance may introduce an asymmetry to the effect of protein oncotic forces on transepithelial volume flow. Peritubular oncotic forces close the interspace, enhance interspace hypertonicity, and thus substantially increase volume reabsorption (enhanced intraepithelial solute-solvent coupling). The model also predicts a decline in epithelial water permeability (Lp), salt reflection coefficient, and salt permeability, with the application of peritubular protein. When parameters are chosen so as to represent the rat proximal tubule, the predicted effect on solute permeability is comparable to the observed changes in electrical resistance of the epithelium. However, when the luminal solution is slightly hypotonic to blood and proximal reabsorption has become isosmotic, the models show relatively small protein effects, which are dependent upon cell and tight junction permeabilities and are little influenced by interspace compliance. The capability of such models to represent the peritubular protein enhancement of isosmotic salt and water reabsorption by the proximal tubule in vivo is questioned.